SULF1在胃癌中的表达及其对细胞增殖的影响

doi:10.3969/j.issn.1673-8640.2025.08.015

摘要/Abstract

摘要：

目的探讨硫酸酯酶1（SULF1）在胃癌中的表达及其对细胞增殖的影响。方法通过基因表达综合数据库（GEO）GSE33335数据集和GSE79973数据集筛选差异表达基因，在癌症基因组图谱数据库（TCGA）中进行验证，选取SULF1基因进行后续分析。通过HPA数据库分析正常胃上皮组织（简称正常组织）和胃癌组织中SULF1的表达情况。通过Kaplan-Meier Plotter数据库分析血清SULF1水平与胃癌患者总生存期的关系。选取2023年8—9月同济大学附属第十人民医院胃癌患者50例（胃癌组）和健康体检者30名（正常对照组），收集所有研究对象临床资料，并检测血清SULF1水平。检测人胃黏膜细胞系GES-1和人胃癌细胞系AGS、MKN-28、MKN-45、BGC-823、SGC-7901中SULF1蛋白和mRNA的表达情况。构建SULF1敲低稳定细胞株（SULF1敲低组），采用CCK-8实验和克隆形成实验分析细胞的增殖能力。结果通过GEO数据库和TCGA数据库分别筛选和验证了6个差异表达最显著的上调基因。HPA数据库免疫组化分析结果显示，胃癌组织SULF1蛋白呈高表达（P<0.05）。胃癌患者血清SULF1水平高于正常对照者（P<0.001）。SULF1高表达组总生存期明显短于SULF1低表达组（P<0.01）。与对照组（阴性对照组稳定细胞株）比较，SULF1敲低组（BGC-823细胞、SGC-7901细胞）SULF-1蛋白和mRNA相对表达量均降低（P<0.001），细胞增殖能力减弱（P<0.001）。结论 SULF1在胃癌中呈高表达，且作为癌基因促进胃癌细胞增殖。SULF1高表达的胃癌患者预后较差。

关键词: 硫酸酯酶1, 胃癌, 生物信息学, 细胞功能

Abstract:

Objective To investigate the expression of sulfatase 1（SULF1） in gastric cancer and its influence on cell proliferation. Methods Differentially expressed genes were screened from the Gene Expression Omnibus（GEO） datasets（GSE33335 and GSE79973） and verified in the Cancer Genome Atlas（TCGA） database. The SULF1 gene was selected for further analysis. The expression of SULF1 in normal gastric epithelial tisssues and gastric cancer tissues was analyzed using the Human Protein Atlas（HPA） database. The relationship between serum SULF1 levels and overall survival of gastric cancer patients was analyzed using the Kaplan-Meier Plotter database. Fifty patients with gastric cancer（gastric cancer group） and 30 healthy subjects（healthy control group） from Tongji University Affiliated Tenth People's Hospital from August to September 2023 were enrolled. The clinical data were collected，and serum SULF1 levels were determined. The expressions of SULF1 protein and mRNA in human gastric mucosal cell line GES-1 and human gastric cancer cell lines AGS，MKN-28，MKN-45，BGC-823 and SGC-7901 were determined. Stable SULF1 knockdown cell lines（SULF1 knockdown group） were constructed，and cell proliferation was determined by CCK-8 assay and colony formation assay. Results Six differentially expressed genes with the most significant upregulation were screened from the GEO database and verified in the TCGA database. Immunohistochemical analysis in the HPA database showed that SULF1 protein was highly expressed in gastric cancer tissues（P<0.05）. Serum SULF1 levels in gastric cancer patients were higher than those in healthy control group（P<0.001）. The overall survival of SULF1 high-expression group was shorter than that of SULF1 low-expression group（P<0.01）. Compared with control group（negative control stable cell line），the relative expression levels of SULF1 protein and mRNA in SULF1 knockdown group（BGC-823 cells，SGC-7901 cells） were decreased（P<0.001），and cell proliferation ability was weakened（P<0.001）. Conclusions SULF1 is highly expressed in gastric cancer and acts as an oncogene to promote gastric cancer cell proliferation. Gastric cancer patients with high expression of SULF1 have a poorer prognosis.

Key words: Sulfatase1, Gastric cancer, Bioinformatics, Cell proliferation

中图分类号:

Q556

徐蕾, 金依颖, 黄楠, 马纪, 潘秋辉. SULF1在胃癌中的表达及其对细胞增殖的影响[J]. 检验医学, 2025, 40(8): 810-816.

XU Lei, JIN Yiying, HUANG Nan, MA Ji, PAN Qiuhui. Influence of SULF1 expression on cell proliferation in gastric cancer[J]. Laboratory Medicine, 2025, 40(8): 810-816.

图/表 8

表1 引物序列

基因名称	正向引物（5'~3'）	反向引物（5'~3'）
SULF1	GATCCCCGAGGTTCAGAGGA	GGTGTAGTCACAAAGGCATTGA
GAPDH	GGAGCGAGATCCCTCCAAAAT	GGCTGTTGTCATACTTCTCATGG

表2 GSE33335数据集和GSE79973数据集的基本信息

数据集	检测平台	样本数/对	年龄/岁	性别
数据集	检测平台	样本数/对	年龄/岁	男/例	女/例
GSE33335	GPL5175	25	65±12	15	10
GSE79973	GPL570	10

图1 胃癌患者差异表达基因筛选的火山图注：（a）GSE33335数据集；（b）GSE79973数据集；表达下调基因，表达上调基因，表达无差异的基因；横虚线表示P<0.05，竖虚线表示|log2 FC|>1。

图2 表达上调基因的筛选和验证注：（a）韦恩图；（b）6个表达上调基因的表达热图；红色为表达上调，蓝色为表达下调；（c）6个表达上调基因在TCGA数据库中的验证结果；与癌组织比较，*P<0.05。

图3 癌组织和正常组织SULF1蛋白表达差异及其与胃癌患者预后的关系注：（a）HPA数据库中正常组织和胃癌组织的免疫组化染色图（×200）；（b）胃癌组和正常对照组血清SULF1水平比较；（c）SULF1高表达组和低表达组的Kaplan-Meier生存曲线；低表达组，高表达组。

图4 各细胞系SULF1表达的比较注：（a）各细胞系SULF1蛋白表达的免疫印迹图；（b）各细胞系SULF1 mRNA相对表达量的比较；与GES-1细胞比较，*P<0.05、**P<0.01、***P<0.001。

图5 SULF1敲减组和对照组SULF1表达的比较注：（a）SULF1蛋白表达的免疫印迹图；（b）SULF1 mRNA相对表达量比较； shCON（对照）， shSULF1-1， shSULF1-2；与shCON（对照）比较，*P<0.001。

图6 SULF1敲低组和对照组细胞增殖情况比较

注：（a）BGC-823细胞CCK-8实验； shCON（对照）； shSULF1-1， shSULF1-2；（b）SGC-7901细胞CCK-8实验； shCON（对照）， shSULF1-1， shSULF1-2；（c）克隆形成实验；（d）克隆形成实验计数结果； shCON（对照）， shSULF1-1， shSULF1-2；与shCON（对照）比较，*P<0.001。

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